The present invention provides novel compounds. More particularly, the present invention provides novel renin-inhibiting peptide analogs. Additionally, the invention herein provides novel intermediates for the preparation of novel renin-inhibiting peptides and novel processes for the preparation of the intermediates and both novel and known renin-inhibiting peptide analogs. Unexpectedly advantageous novel peptide analogs are also the present invention. The renin inhibitors provided herein are useful for the diagnosis and control of renin-dependent hypertension.
Renin is an endopeptidase which specifically cleaves a particular peptide bond of its substrate (angiotensinogen), of which the N-terminal sequence in equine substrate is for example: ##STR1## as found by L. T. Skeggs et al, J. Exper. Med. 106, 439 (1957). Human renin substrate has a different sequence as recently discovered by D. A. Tewkesbury et al, Biochem. Biophys. Res. Comm. 99, 1311 (1981). It may be represented as follows: ##STR2## and having the sequence to the left of the arrow (.dwnarw.) being as designated in formula IA as above.
Renin cleaves angiotensinogen to produce angiotensin I, which is converted to the potent pressor angiotensin II. A number of angiotensin I converting enzyme inhibitors are known to be useful in the treatment of hypertension. Inhibitors of renin are also useful in the treatment of hypertension.